Background
Adrenocortical carcinoma is a rare malignancy of the adrenal cortex with an estimated annual incidence of one to two per million population per year. Patients often present with rapid disease progression. The current mainstay of treatment for metastatic disease is with mitotane plus combination chemotherapy; however, mortality remains high and further options are needed.
Case
A 74-year-old-woman was incidentally noted to have an adrenal lesion measuring 30x21x30mm with a non-contrast density of 30HU in early 2018 upon investigation of shortness of breath. A repeat CT abdomen/pelvis performed 4 months later showed doubling of the adrenal lesion size to 56mm with a density of 40HU. Hormonal testing was unremarkable. She underwent surgical resection with histopathology confirming a 90mm adrenocortical carcinoma with extracapsular extension and vascular invasion but no involvement of the removed 15 lymph nodes. Microscopy reported aggressive features including high mitotic activity with ki67 index of 40% and negative staining for DNA mismatch repair proteins MSH2 and MSH6. She was treated with mitotane therapy for 2 months but an FDG-PET scan demonstrated multiple new glucose avid abdominal lymph nodes and pulmonary metastases with the largest lesion measuring 20mm in the right middle lobe. She was administered a single dose of ipilimumab and nivolumab after which she developed immune-related hepatitis. On serial imaging she demonstrated impressive response with reduction in size of the pulmonary lesions and has subsequently remained clinically and radiologically stable after 3 years.
Discussion
There have been clinical trials assessing the use of immune checkpoint inhibitors with varying results. The key predictors of response appear to be tumour factors including microsatellite instability, PDL-1 positivity and mismatch repair abnormalities. Therapies such as IGF1 receptor inhibitors, VEGF inhibitors and EGFR inhibitors have provided disappointing results to date. This case help illustrate the emergence of newer, more effective treatment options.